Nutrient antacid composition and method of making the same



June 14, 1960 B. R. wElNsTElN 2,940,897

NUTRIENT ANTAOIO COMPOSITION ANO METHOD OF MAKING THE SAME:

Filed May 8, 1956 E??? fj i2 0 20 4g 60 80 lao 12a /40 /60 /80 200 m f 0./040 N. H

mln; 0.1040 lV. HC' INVENTOR Patented June 14, 1960 NUTRIENT ANTACID COlVIPOSITION AND METHOD OF MAKING THE SAL/IE Filed May 8, 1956, Ser. No. 583,419 12 Claims. (Cl. 167-55) This invention relates to antacids, i.e., pharmaceutical chemical products for neutraling hyperacidity in the stomach and intestines. More particularly, it contemplates a reaction product prepared from milk proteins and an antacid chemical and'possesses both nutritional and therapeutic properties. A number of alkaline compounds have long been employed for the purpose of more or less neutralizing the acid juices of the stomach. This class or group of chemicals are known, in medical terminology, as antacids. Typical antacids are calcium carbonate, lime-water, milk of magnesia, aluminum hydroxide, magnesium carbonate, and sodium bicarbonate. All of the antacids are capable of serving, with proper dosage, to elevate the pH of the contents of the stomach for a period of time depending upon the alkalinity or buffering characteristic of the particular antacid or antacids used and the amount of the dosage. Unfortunately, many of these agents are harsh in their action and side effects, dilering with dif ferent individuals, limit their usefulness. Such undesirable side effects may include constitpation Aor purgation and, particularly with 'bismuth compounds, the formation of hard or black stools. The blending of two or more different antacid agents has been employed with limited success in an attempt to counter the side effects. It has not been possible to satisfactorily control, in this way, the undesirable reactions mentioned above or to prevent the irritation of mucous tissues.

The principal object of the invention herein described is to provide an antacid composition which, when taken into the stomach, will neutralize and buier stomach liquids and maintain, over a relatively prolonged period of time, a level of acidity which is satisfactory in almost all instances where neutralization Iby an external agent is indicated while, at the same time, avoiding alkalizing to such an extent that digestion cannot proceed properly.v A further object is to provide an antacid composition of this character, the use of which is not accompanied by more than easily tolerable side effects. Additional advantageous characteristics reside in the nutritional value ofthe material itself, the uniformity of results with different individuals, avoidance of mucous membrane irritation, and gentleness and uniformity of action throughout the sphere of inuence. The antacid composition may be intimately mixed with other therapeutic materials, such as aspirin, without adverse effect on such materials as experienced with ordinary antacid agents. Additionally, and of considerable importance, hyperacidity can be controlled without inducing a residual alkaline condition.

The antacid composition is the reaction product of aV milk protein or mixtu-re of proteins derived from milk and an antacid reagent. The principal milk proteins are casein and lactalbumin. Other proteins are also present in much smaller quantities and are generally present with commercially prepared albumin. All of these proteins are useful in the preparation of the antacid composition described herein. 'lhe preferred product is made from lactalbumin, and satisfactory products may be prepared from a mixture of lactalbumin and casein, or from casein alone. Preference for the albumin-base product reflects the somewhat superior acid-absorbing properties of this composition.

Any of the members of the class of chemical reagents known as antacids may be used for reaction with the protein material in the preparation of the buffering antacid composition. I'he following compounds are listed by way of examples of suitable antacid reagents: calcium carbonate, calcium lactate, calcium sulfate, calcium hydroxide, calcium gluconate, aluminum hydroxide, magnesium hydroxide, magnesium trisilicate, magnesium carbonate, sodium carbonate, sodium bicarbonate, ammonium hydroxide, bismuth subnitrate, bismuth subcarbonate, and bismuth subgallate.

Reaction of the antacid chemical compound with the protein is accomplished lby mixing the -antacid reagent with a water slurry of the protein in the form which may be called activated or solubilized, and cooking the mixture at a temperature of between to 190 F. for a period of time sucient to bring about the desired reaction as indicated by the gradual transition of the entire mass to the consistency of a heavy paste. Since the pH of the cook changes gradually as the reaction proceeds during the cooking process, the end point may be determined by pH, predetermined for a given recipe. T-he time required for the reaction varies with the temperature of the cook and the reactivity of the particular antacid constituent. The resulting product may be dried by known processes, such as spray or roller drying.

A suitable raw protein material is thecoprecipitated casein-lactalbumin prepared by the process described n Patent No. 2,623,038 of Everette C. Scott. 'This product is a casein-lactalbumin fusion which must be activated preliminarily to the reaction with the antacid reagent. This may be accomplished by the method described in Patent No. 2,832,685 of Everette E. Scott, whereby a water slurry of the -fusion is alkalized by means of a strong alkali, such as potassium hydroxide, to a pH of 6.6 to 6.7, a volatile alkali, such as ammonium hydroxide, is added to bring the pH to approximately 8.4 to 8.5, and the mixture is heated to a temperature of between F. and 212 'F. to hydrate the protein and render the same dispersable and activated, ready for the reaction with the antacid chemical.

As a specific example of a satisfactory process for the preparation of the nutrient antacid composition of this invention from skim milk, the following complete and detailed specification is given:

The skim milk is delivered such as a conventional cheese normal titratable acidity, measured as lactic acid, is 0.16% to 0.18%. The titratable acidity is adjusted downwardly lby the addition of a suitable alkalizing material to a point where the titratable acidity ranges between 0.16% and 0.1%. Sodium bicarbonate or soda ash, or a combination of these two materials, are suitable for this acidity reduction. The milk is then heated to a temperature ofv between to 194 F. The application of heat and agitation of the milk is then discontinued and dilute hydrochloric acid is added to bring about .the complete precipitation i of all casein, lactalbumin and lactoglobulin fractions of the milk. The result is a homogeneous mass of precipitated protein.

The whey is withdrawn from the vat. The precipitated protein is then washed with hot water until all or practically all of the whey is removed. The washto a suitable receptacle ing is usually accompanied by the breaking up of the vat. At this point, the

Albumin,

terial is 5.7 to 5.8. A strong alkali, such as potassiumV 'hydroxide is added tothe slurry tobring the pH to 6.6

toA 6.7 and a. Volatilev alkali, such. asY ammonium hydroxide, is addedl to bring the pH to about 8.3 and the slurry isheated to a temperature of about 170 F. to-180 F., at which .temperature Ithe proteinmaterialis'hydrated to an activated state, ready for? the 'antacidl reaction.

which is. prefer-red for the purposen of preparing the protein for reaction inlacc'ordance with the 415 Y- It should be understood' that'` the foregoing outline of Y procedure is that invention.. Variations and alternativesofprocedure for activation ofthe protein' materialmayrbeemployed. VTo. thisV slurry, aV selected antacid" reagent, as; for exi. ample, calcium carbonate, is added inthe form ot a'solution of this chemical. The relativeproportions'of proteinrandi calcium carbonate may vary from. about-5V parts Y of calcium'carbonate andV 95. partso protein solids,.to about1160 parts of calcium carbonateV and; 4.0 parts of proteinsolids'- T hismixture' is held at a temperature of about; 170 F. ,for a period ofabout 30 minutes, which is approximately the length of; time necessary toY complete lthe reaction of this particularY combination. This reaction-:product is then comminuted and `dried :by known techniques,` such asspray drying; The resulting product isa nutrient antacid 'composition offthis invention.

. 4 Albumin, 3 parts, magnesium trisilicate, 2 parts, aluminum hydroxide, 3 parts Albumin, 2 parts, bismuth subnitrate, 1 part, aluminum hydroxide, 1 part g Albumin, 2 parts bismuthA subcarbonate, 1 part, aluminum hydroxide, 1 part It should ber,herefpointediout;that` the reactionof protein and antacid' reagent does not' appear to involve a stoichiometric relationship;v Consequently, the `relative proportions of reacting materials vary without critical limitations. The presence ofi both classes of such materials, under Ythe conditions herein speciiied, results in chemical reactit'n and tlieproduction f the desired antacid reactionV product composition, this Ebeing the objective and accomplishment of the invention. Free antacid reagent, or unreactedrprotein, present in the iinal productV along-with lthereactioncompositiomis not necessarily undesirable and may?, Y inffaci. be., desirablel toY meet particular-requirements. 'Lheadvantageous characteristics of.- the invention are available ,and manifested when; an appreciable amountoftthereaetion.'composition is present y in the product, and this conditionniayfreasonablybev conv Asa further example of a processY for making a pre- Y,

ferred` antacid composition from/ commercially availableYlactalbumin, the following' specication is given:

A 300 gal.V kettle equipped; with'a doublej-acting'agitatorvis supplied to about 2/3 of lits capacity With ywater and 22.8 ounces of sodium hydroxide is added and dissolved(- To-this solution, 100 pounds of denatured granular albumin is` added and the slurry heated -to 170 F. Sulticient ammonium hydroxideis then added to elevate the pHof the slur-ry', to between 94 and 10.5t. Themix- -tureeis desirably heated -to about 175 F. One hundred pounds Votaluminum hydroxide dry. gel' (a commercially available antacicl` preparation) isradded andthe contents of, the kettle .permitted to .react at the elevated temperature tor-a period ofl about minutes: The product is thenpumped.throughahammer mill and placedin a re-v ciculating storage tank and spray dried.- '1'.he..dry ant-Y acidcomposition. resulting. from this process exhibits a pH of from 9.4 to 9.8.

It'willbe understood that the reaction yof the protein-Y andV anta'cd reagent may befcarried out at temperatures other than those given -inthefforegoing examples. In generaLthe desirable temperature Vrange is between 140"V vto 199` E., 'the time required for reactionV depending upon the temperature of the `reaction mass as Well as the natureof the particular-reagents usedi .TlieatollowingV examples-oi recipes indica-te ranges ofiv relative proportions of ingredientsithathavebeernfound to produce useful products:

AlbumingS parts, aluminum-hydroxide, 1 part Alb'umim'l part, aluminum? hydroxide, 3 parts' 3' parts, 'magnesium trisilicate; "5' parts Albumin, 5' partaxmagneSium trisilicate, 31 parts. Albumin,"7fparts, calcium lactate, Yl' part Y Albumin, Sparta, calcium lactate, '5r parts? Albumin, 3 parts,V calcium'carbonate, 5k parts'.V Albumin, 3 parts, calciumV carbonate', 2 parts Albumin, 3V parts', magnesium trisilicate, 3 parts, aluminum hydroxide,'2 parts Y Albumimiz parts, magnesium-trisi-licata parts, aliunY num hydroxide, 3 parts Vantacid 4reagentisused with 95 pai-ts of protein.

lrnthe accompanyingdrawing the-neutralizing or butiering '.rharacteristicsY uncertain: antacidsare shown and comparedV with the. buiering action. of the-1 react-ionv product.v of theinvention. In each of these graphs, any given pointon the curveshowsytor. a given sample of antacid, the pH (on the, ordinate scaleywhen the number of milliliters. of.' 0.1040 N hydrochloric acid (shown on the abscissascale) has beenfaddedA tolthe sample.

-In Fig, 1, the. pH' of 10D milliliters ofV water containing 3 gms. of calcium carbonate. isV shown at the several titration 'increments of the' hydrochloric acid. solution. AnV excessively high; (for thestoniach) levelY o'f'lalkalinity is maintained., y

Forcomparisoh'prposes, v two graphs are. 'shown in Eig.v 2. rIlle-dotted line i'sthe tititioncurve' for 11/2 gms. ofrvcalc'ium carbonate"in 100 millilites of Water, into which 11/2 of solubiliz'ed or activated lactalbumin have been stirred without heating;v i2e;, a mix of equal" parts' of activatedalbumn vand' calciumV carbonate placed in water for titration purposes. Thesolid line is the titration curve' for 3` of thereaction product prepared from equalpartsofactivated albuminl and calcium carbonate'fasgabove described. The sustained bufferingV action of the'reactionV product, as compared'with that of thev corresponding Aunrea'ctedr mixture, is apparent.

The' comparative titration curvesof Fig. 3Y are similar to those of Fig. 2, except that aluminum ,hydroxide is used as the a'ntacicl chemical in place of calcium carbonate. The butlfening1 or acid-absorbingA proper-ties of the reaction product arey se'enrto` greatly exceed the correspondingY reactionY of theY unreacted mixture. y Equal' parts of activatedalbuminY andammonium'hydroxide were usedV in' tion of the'reaction',productgpandthe'coricentrationl iny both instances was 3 per" 10Q millilitersz lt willbe, understoodlthat;whilethebufering capacity otra reaction productjof theY invention Will'vary'withV ditering reagentsl and' proportions VthereofiusedV in its prenaraiilii" ,Y which permits 'thefproduc't'ion" off' a` vseriesv of compositions cludeA somef unreaot'ed-v protein Y r'natferialY or unreacted;

antac'id reagent; but thefpresence'S-iofisuch materialy doesV not interfrerelwith the b'eing-actionl of Utile antacid reaction 'pr'odfuctr I clirh1 1. The method 0f making .a nutrient antacid composithe'unreacted'fmixture andin the prepara# ,this isfaesirable--ia that it snersnenbnity tion which comprises cooking a mixture of an antacid and a processed milk protein in a Water slurry, said milk protein having a pH of from about 8 to about 10.5 and being the product of acid precipitation followed by alkali solubilization at an elevated temperature; and continuing said cooking at a temperature of at least about 140 F. for a period of time suicient to effect reaction as indicated by conversion of the slurry to a heavy pasty mass.

2. The method of making a nutrient antacid composition which comprises cooking a mixture of an antacid and a processed milk protein in Ia Water slurry, said milk protein having a pH of from about 8 to about 10.5 and being the product of acid precipitation followed by alkali solubilization at an elevated temperature; and continuing said cooking at a temperature of from about 140 F. to about 190 F. for a period of time sufficient to eiect reaction as indicated by conversion of the slurry to a heavy pasty mass.

3. A nutrient antacid composition comprising a reaction product of a processed milk protein and an antacid, said milk protein being the product of acid precipitation followed by alkali solubilization at an elevated temperature; sad protein at a pH of about 8 to about 10.5 being reacted with the antacid at a temperature of at least about 140 F.

4. A nutrient antacid composition comprising a reaction product of a processed milk protein and an antacid, said milk protein being the product of acid precipitation followed by alkali solubilization at an elevated temperature; said protein at a pH of about 8 to about 10.5 being reacted with the antacid at a temperature of at least about 140 F., said product being characterized in that it exhibits a greater buffering eect than that of its unreacted constituents.

5. A nutrient antacid composition comprising a reaction product of a processed milk protein and a calcium salt selected from the group consisting of calcium carbonate, calcium lactate, calcium sulfate, calcium hydroxide and calcium gluconate, said milk protein being the product of acid precipitation followed by alkali solubilization at an elevated temperature; said protein at a pH of about 8 to about 10.5 being reacted with the calcium salt at a temperature of at least about 140 F.

6. A nutrient antacid composition comprising a reaction product of a processed milk protein and an aluminum hydroxide, said milk protein being the product of acid precipitation followed by alkali solubilization at an elevated temperature; said protein at a pH of about 8 to about 10.5 being reacted with the aluminum hydroxide at a temperature of at least about 140 F.

7. A nutrient antacid composition comprising a reaction product of a processed lactalbumin and an antacid, said lactalbumin being the product of acid precipitation from skim milk followed by alkali solubilization at an elevated temperature; said lactalbumin at a pH of about 8 to about 10.5 being reacted with the antacid at a temperature of at least about F.

8. A nutrient antacid composition comprising a reaction product of a processed lactalbumin and a calcium carbonate, said lactalbumin being the product of acid precipitation from skim milk followed by alkali solubilization at an elevated temperature; said lactalbumin at a pH of about 8 to about 10.5 being reacted with the calcium carbonate at a temperature of at least about 140 F.

9. A nutrient antacid composition comprising a reaction product of a processed lactalbumin and an aluminum hydroxide, said lactalbumin being the product of acid precipitation from skim milk followed by alkali solubilization at an elevated temperature; said lactalbumin at a pH of about 8 to about 10.5 being reacted with the aluminum hydroxide at a temperature of at least about 140 F.

l0. A nutrient antacid composition comprising a reaction product of a processed lactalbumin and a calcium salt selected from the group consisting of calcium carbonate, calcium lactate, calcium sulfate, calcium hydroxide and calcium gluconate, said lactalbumin being the product of acid precipitation from skim milk followed by alkali solubilization at an elevated temperature; said lactalbumin at a pH of about 8 to about 10.5 being reacted with a calcium salt at a temperature of at least about 140 F.

1l. A nutrient antacid composition comprising a reaction product of a processed casein and an antacid, said casein being the product of acid precipitation from skim milk followed by alkali solubilization at an elevated temperature; said casein at a pH of about 8 to about 10.5 being reacted with the antacid at a temperature of at least about 140 F.

l2. A nutrient antacid composition comprising a reaction product of an antacid and a processed coprecipitate of casein and lactalbumin, said coprecipitate being the product of acid precipitation from skim milk followed by alkali solubilization at an elevated temperature; said protein at a pH of about 8 to about 10.5 being reacted with the antacid at a temperature of at least about 140 F.

Lipschitz Nov. 7, 1944 Paterson Oct. 25, 1955 

1. THE METHOD OF MAKING A NUTRIENT ANTACID COMPOSITION WHICH COMPRISES COOKING A MIXTURE OF AN ANTACID AND A PROCESSED MILK PROTEIN IN A WATER SLURRY, SAID MILK PROTEIN HAVING A PH OF FROM ABOUT 8 TO ABOUT 10.5 AND BEING THE PRODUCT OF ACID PRECIPITATION FOLLOWED BY ALKALI SOLUBILIZATION AT AN ELEVATED TEMPERATURE, AND CONTINUING SAID COOKING AT A TEMPERATURE OF AT LEAST ABOUT 140* F. FOR A PERIOD OF TIME SUFFICIENT TO EFFECT REACTION AS INDICATED BY CONVERSION OF THE SLURRY TO A HEAVY PASTY MASS. 